An oral preparation is a dosage form most frequently used among pharmaceutical products. Many oral preparations capable of maintaining drug efficacy with the administration of once or twice a day have been developed in recent years to improve QOL. While synthesis of compounds showing kinetics of sustained drug efficacy with the administration of once or twice a day has been tried in the synthetic stage of the compound itself, the kinetics are quite often modified by designing a long acting preparation with ingenuity in formulation.
As the dissolution property of a long acting preparation, which is suitable for prolonged blood concentration of a drug, zero-order release has been reported. This is based on an idea that, when absorbability of a drug from the gastrointestinal tract does not show changes depending on the absorption sites, prolonged drug concentration in plasma can be achieved by releasing the drug at a constant rate over the whole area in the gastrointestinal tract (small intestine, large intestine) after taking a preparation. However, the inside of the gastrointestinal tract is not the same, and pH, amount of digestive juice, mechanical force on the preparation, effective surface area and the like vary depending on the sites. Thus, a preparation that shows zero-order dissolution in an in vitro dissolution test does not necessarily show similar dissolution property and absorbability in the gastrointestinal tract. Depending on the kind of the drug to be an active ingredient, the blood concentration cannot be maintained within an effective therapeutic range for a long period of time. Therefore, a development design of a long acting preparation, which is based on a different release-control strategy suitable for drug property and environment in the gastrointestinal tract, has been desired (e.g., WO 99/51209, JP-B-6-11699, JP-A-9-143073, Eur. J. Pharm. Sci., 1: 195-201 (1994)).
Controlled release preparations containing, as an active ingredient, a compound having a proton pump inhibitory activity such as omeprazole and the like are generally described in some literatures (US 2002-0051814, JP-A-2002-532425). However, there is no report yet on the release-control strategy that should be employed to achieve desired sustained drug efficacy.
It is an object of the present invention to provide a long acting preparation, wherein the release of the active ingredient (e.g., proton pump inhibitor) is controlled in multisteps, and the active ingredient is released in the gastrointestinal tract over a long period of time.